Skip to Content
Merck
CN
  • Identification of ICAT as an APC Inhibitor, Revealing Wnt-Dependent Inhibition of APC-Axin Interaction.

Identification of ICAT as an APC Inhibitor, Revealing Wnt-Dependent Inhibition of APC-Axin Interaction.

Molecular cell (2018-09-11)
Lei Ji, Bo Lu, Zhizhi Wang, Zinger Yang, John Reece-Hoyes, Carsten Russ, Wenqing Xu, Feng Cong
ABSTRACT

Adenomatous polyposis coli (APC) and Axin are core components of the β-catenin destruction complex. How APC's function is regulated and whether Wnt signaling influences the direct APC-Axin interaction to inhibit the β-catenin destruction complex is not clear. Through a CRISPR screen of β-catenin stability, we have identified ICAT, a polypeptide previously known to block β-catenin-TCF interaction, as a natural inhibitor of APC. ICAT blocks β-catenin-APC interaction and prevents β-catenin-mediated APC-Axin interaction, enhancing stabilization of β-catenin in cells harboring truncated APC or stimulated with Wnt, but not in cells deprived of a Wnt signal. Using ICAT as a tool to disengage β-catenin-mediated APC-Axin interaction, we demonstrate that Wnt quickly inhibits the direct interaction between APC and Axin. Our study highlights an important scaffolding function of β-catenin in the assembly of the destruction complex and suggests Wnt-inhibited APC-Axin interaction as a mechanism of Wnt-dependent inhibition of the destruction complex.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone B-5-1-2, purified from hybridoma cell culture
Sigma-Aldrich
Anti-APC (Ab-1) Mouse mAb (FE9), liquid, clone FE9, Calbiochem®